2beta-halo-17alpha-alkenyl-19-nor-androstane-3alpha, 17beta-diols



3,169,136 ZB-HAIiG-flu-ALKENYLJQ-NOR- ANDROSTANE-3oc,17fl-DIOLS AlbertBowers and John Edwards, Mexico City, Mexico,

assignors, by mesne assignments, to Syntax Corporation, a corporation ofPanama No Drawing. Filed Feb. 14, 1962, Ser. No. 173,135

3 Claims. (Cl. zen-397.5

The present invention relates to novel cyclopentanophenanthrenederivatives and to a process for the production thereof. 7

More particlarly the present invention relates to novelZfl-halQ-androstan-Bu-ol derivatives.

The novel compounds of the present invention are represented by thefollowing formulas:

RZO--- 2 up to carbon atoms, acyloxy containing up to 12 carbon atoms,nitro, amino or halogen. Typical ester groups are theacetate,propionate, enanthate, benzoate, trimethylacetate, t-butylacetate,phenoxyacetate, cyclopentylpropionate, .aminoaoetate and,B-chloropropionate.

The compounds represented by the above formulas are anabolic-androgenicsubstances with a favorable anabolicandrogenic ratio, and exhibit antiestrogenic and antigonadotr-ophic activities. In addition, thesecompounds "possess useful blood cholesterol lowering and anti-fibril--lator'y properties, and inhibit the action of the pituitary gland.

Thenovel compounds, objects of this invention, may be produced by theprocess illustrated by the following equation:

'tives (VII 3,15%,336 Fatented Fete. ii, I955 OR OR R R X- X v1 vrrr Inthe above formulas R, R R and X havethe same meaning as hereinbefore setforth and R represents lower alkyl, lower alkenyl or lower alkynyl.

In practicing the above outlined process the starting A -androsten-170neor 19-nor derivative thereof (1) is treated with an organic peracid,preferably 1nonoperphthalic acid, to produce2a,3ct-oxido-androstan-l7-one or the 19-nor derivative thereof (11).Opening of the epoxide ring of the latter compoundswith a hydrogenhalide in a suitable solvent, is productive of the corresponding 2halo-androstan-3a-ol-17-one compounds (III: R =H) which uponconventional reaction with dihydropyr-ane in .the presence of an acid,such as p-toluene sulfonic acid in an inert solvent, preferably benzene,yield the respective 3-tetrahydropyranyl ether derivative, (IV).Reduction of the 17-keto group of the latter compound e.g.,

With sodium borohydride, furnishes the corresponding 1'75- hydroxyderivative (V: R I-I) which upon a conventional acylation followed byacid hydrolysis yields the 17/3-acyloxy-3a-hydr0xyl compound (VI:R=acyl; R =H). Basic hydrolysis or double metal hydride reduction isproductive of the 3a,17B-free diol (VI: R=R =H). v

The 17-keto compounds represented by formula (IV), when treated withlower alkyl, lower alkenyl or lower alkynyl magnesium halide, e.g.,methyl magnesium bromide, vinyl magnesium bromide, or ethynyl magnesiumvbromide, yields the respective 17a lower (alkyl', alkenyl -or alkynyl)17,8 hydroxy deriva- CQnVentional acylation in the presence of p-toluenesulfonic acid is productive of the 301,176- di-acylatesXVIII: R=R =acyl)which upon mild alkaline "hydrolysis give the 3 x-free alcohols (VIII:R=acyl;

R =H). Reduction with lithium aluminum hydride affords the corresponding3a,17B-free-diols (VIII; R=R :H).

The compounds described hereinbefore having one or two secondaryhydroxyl groups present in the molecule (III, V, VI, VIII: R=R =H) 'areconventionally esence of p-toluenesulfonic acid, with an acylating agentto u give the corresponding Hot-substituted -17/3-acylate (VIII:R=acyl). The acyl group at C-17 may be the same as or different to theacyl group at C3.

The following specific examples serve to illustrate, but are notintended to limit the present invention:

Example I A solution of 2.5 g. of A -androsten-l7-one (Hirschmann. J.Biol. Chem. 136, 448, (1944)) in 100 cc. of chloroform was cooled to C.and mixed with 1.1 molar equivalents of monoperphthalic acid in ethersolution. The mixture was kept at room temperature for 20 hours, dilutedwith water, the organic layer was separated, washed with aqueous sodiumbicarbonate solution and then with water to neutral, dried overanhydrous sodium sulfate and evaporated to dryness. Crystallization fromacetone-hexane gave 2a,3oc-oxido-androstan- 17-one.

By the same procedure l9-nor-A -androsten-17-one (Bowers et al. US. p.appl. Ser. No. 128,361, filed August 1, 1961) was converted into:2a,3a-oxido-l9- nor-androstan-17-one.

Example II ture Was stirred at a temperature lower than 10 C. for

6 additional hours, then neutralized by cautiously adding a aqueoussodium bicarbonate solution and transferred to a separatory funnel. Theorganic layer was Washed with water, dried over anhydrous sodium sulfateand concentrated until formation of an abundant precipitate. The mixturewas cooled, the precipitate filtered and redissolved in hot ethylacetate, the insoluble material was filtered off and the filtrate cooledwhereby there crystallized Qfl-fluoro-androstan-3a-ol-17-one.

When applying the above procedure to 2a,30c-0Xid0l9-nor-androstan-17-one, there was obtained 2 8-fluoro-19-nor-androstan-3a-ol-17-one.

Example III To a solution of 4 g. of 2e,3a-oxido-androstam17-one, in 40cc. of anhydrous chloroform, was added, over a period of 35 minutes, 30cc. of a 0.45 N solution of dry hydrogen chloride in chloroform, undercontinuous tirring and maintained the temperature arount 0 C. The

mixture was then stirred at 0 C. for 8 hours further,

diluted with water and the chloroform layer was separated, washed withaqueous sodium bicarbonate solution and then with water, dried overanhydrous sodium sulfate and evaporated under reduced pressure.Crystallization of the residue from acetone-hexane gave2,8-chloroandrostan-3a-ol-17-one.

211,3a-oxido-19-nor-androstan-17-one was treated following the aboveprocedure, to give 2fi-chloro-l9-norandrostan-3ot-ol-17-onee Example IV2a,3a-oxido androstan-17-one and 2a,3a-oxido-l9-norandrostan-l7-one weretreated following the procedure described'in the foregoing example,except that hydrochloric acid was substituted by hydrobromic acid, thusyielding respectively 25 bromo-androstan-3a-o1-l7-one and2,8-bromo-19-nor androstan-3a-ol-17-one.

7 Example V A mixture of 2 g. of 2a,3ot-oxido-androstan-17-one, 2

.cc. of ,hydriodic acid and 50 cc. of anhydrous methanol .was refluxedfor 3 hours. It was then cooled and poured intowater. The resultingprecipitate was filtered off,

washed with water and dried. Recrystallization from methylenechloride-hexane furnished 2,13-iodo-androstan- 3a-ol-17-one.

By the same procedure was treated 2u,3a-oxido-19-norandrostan-17-one,thus giving, Zli-iodo-l9-nor-androstan- 3ot-ol-l7-one.

Example VI 10 cc. of dihydropyrane were added to a solution of 5 g. of2;8-fluoroandrostan-3a-ol-17-one, in cc. of benzene and about 5 cc. weredistilled to remove moisture. 1.5 g. of p-toluenesulfonic acid wereadded to the cooled solution, which was then allowed to stand at roomtemperature for 4 days. The solution was washed with sodium carbonateand water, dried and evaporated. The residue was chromatographed on 75g. of neutral alumina. Crystallization of the fractions eluted withhexane from pentane yielded the 3-tetrahydropyr-anylether of2,8-fluoro-androstan-3a-ol-l7-one.

The starting compounds under I were treated by the foregoing procedure,thus giving the corresponding products under II.

2fi-fluoro-l9-nor-androstan-Ba-ol-IT- one.

2fl-ehloro-androstan-3a-ol-17-one The 3-tetrahydropyranylether of2flfluoro-19-nor-androstan-3aol-17-one.

The 3-tetrahydropyranylether of 2B-chloro-androstan-3a-ol-17- one.

The 3 tetrahydropyranylether of 2B-chlero-l9-nor-andr0stan3aol-17-one.

The 3-tetrahydropyranylether of 2,3-bromo-ar1drostan-304-01-17- one.

The 3-tetrahydropyranylether of 2B-bromo-19-nor-androstan-3aol-17-one.

The 3-tetrahydropyranylether or 2B-iodo-19-norandroStan-3a-ol- 17-0ne.

Example VII A solution of 2 g. of sodium borohydride in 30 cc.

of methanol was added with stirring to a solution of 2 g.

of the 3-tetrahydropyranylether of ZB-fluoro-androstan- 3-a-ol-17-one,in 40 cc. of tetrahydrofuran. The mixture was kept at room temperatureovernight, the excess reagent was decomposed by addition of acetic acid,the repounds listed below, to give the corresponding productshereinafter disclosed.

Starting Compounds Products The 3-tetrahydropyranylether of2,6-fluor0-19-nor-androstan- 3a-ol-17-one.'

The Stetrahydropyranylether of 2fi-ehlor0-androstan-3wol- -one.

The S-tetrahydropyranylether of 2B-ehloro-ltl-nor-androstan-3a-ol-17-one.

The 3-tetrahydropyrauylether of ZB-bromo-andr0stan-3z-ol- 17-0nc.

The S-tetrahydropyranylether of 2B-bromo-lflnor-androstan-3nz-0l-l7-OI19.

The B-tetrahydropyranylether of Qfl-iodo-androstan-lia-ol- 17-one.

The S-tetrahydropyranylether 0t 2fliod0-l9-nor-androstan- 3wol-17-ohe.

The 3-tetrahydropyranylether of 2B-fiuoro-l9uor-androstane 311,176-di0l.

The Btetrahydropyranylether (1)1 2fl-phlloro-androstane-3a,

The 3-tetrahydropyranylether of 2fl-chloro-19-nor-andr0stanc-3cz-17fl'di0l.

The 3-tetrahydropyranylether 1 of 2 3,bromo-androstane-3a,

17fi-diol.

The 3 tetrahydr0pyranylether 0t ZB-bromo-l -nor-androstane- TheB-tetrahydropyranylether of 2fl'iodo-androstane-3a- -diol.

The 3-tetrahydropyranylether of 2B-iodo 19-n0randrostane-3a-17B-diol.

Example VIII A solution of 5 g. of the 3-tetrahydropyran ,lether of2fi-fluoro-androstan-3u-ol-17-one in 250 cc. of thiophenefree benzenewas treated with 27.5 cc. of 4N methylmagnesium bromide in ether and themixture refluxed with the exclusion of moisture for 3 hours.

The cooled mixture was cautiously treated with excess aqueous ammoniumchloride solution and the product isolated by ethyl acetate extraction.

The extract was washed with water, dried over anhydrous sodium sulfateand evaporated to dry- HESS.

Recrystallization from methylene chlorideexane afforded the3-tetrahydropyranylether of2fi-flUOI'O-17ocmethyl-androstane-Ba,17t3-diol.

Upon treatment by the same procedure of the starting compounds under I,there were obtained the products under H.

The 3-tetrahydropyranylether of 2fi-fluoro-19-nor-androstan-3a-ol-17-one.

The 3-tetrahydropyrauylether of ZB-chloroandrostan-3a-ol-17-0ne.

The 3-tetrahydropyranylether of '25-chloro-19-norandrostan-3a-ol-17-one.

The 3-tetrahydropyranylether of 2B-brom0-androstan-3a-01-17-one.

The B-tetrahydropyranylether of 2B-bromo-l9-nor-androstan-3a-ol- None.

The 3tetrahydropyranylether of 26-i0do-andr0stan-3ct-ol-l7-one.

The Stetrahydropyrauylether of 2B -i0do -19 -nor endrostan -3a -ol17-0ne.

The 3-tetrahydropyranylether of 2B-ehloro-lM-methyl-androstane- 301,17fl-di0l.

The 3-tetrahydropyranylether of 2 -chloro -17or -methyl-19 -nor -androstane-3a, l7fl-dio1.

The 3 tettahydropyranylether of The 3-tetrahydropyranylether of2,8-bro1no-17a-methy1-19-nor-androstane-3a, 17/S-dio1.

The 3-tetrahydropyranylether of 2,8 -iodo -170c methyl -androstane 3a,17B-di0l.

The 3-tetrahydropyranylether of 2 8 -iodo -17a -methyl -19 -nor -androstane-3n, lifl-diol.

Example IX The 3-tetrahydropyranylether of Z-fi-fluoroandrostan-3OL-Ol.-17-G1'1 was treated following the procedure described in theforegoing example, but using vinyl magnesium bromide instead of methylmagnesium bromide,

thus giving the 3detrahydropyranylether of2,8-fluoro-l7otvinyl-androstane-3 x, 17 fi-diol.

Using exactly the same conditions were treated the starting compoundslisted below, thus yielding the cone sponding products hereinafter setforth.

Starting Compounds Products The B-tetrahydropyranylether of2B-fluor0-19-nor-androstan-3a-ol- 17-one.

The 3-tetrahydropyranylether of Zfl-chl0ro-androstan-3a-ol-17-one.

The 3-tetrahydropyranylether of QB'ehloro-19-nor-androstan-3aol-17-0ne.p

The 3-tetrahydropyranylether of 25 Momo androstan-3a-ol-17-0ne.

The Hetrahydropyranylether of 2,8-bromo-IQ-nor-androstan-M- ol-17-one.The E-tetrahydropyranylether of 2d-iodo-androstan-aa-ol-ll-one. V

The d-tetrahydropyranylether 0t 2fii0do-19-nor androstan3a-ol 17-0ne.

The 3-tetrahydropyranylether 0t2fi-fluoro-17a-vinyl-lQ-norendrostane-bad'iti-diol.

The 3-tetrahydropyranylether 0t 2,6-chloro l7a-vinyl-androstane-3a,17t3-diol.

The S-tetrahydropyranylether ofQB-chloro-l7a-viny1-19-norandr0stane-3a,175-di0l.

The 3-tctrahydropyranylether of of2B-bromo-l7et-vinyl-androstane-3a,l7fi diol.

The 3-tetrahydropyranylether of ZB-br0mo-17a-vinyl-19-n0r-' androstauehdm-diol.

The '3-tetrahydropyranylether of 2B-iodo-17q-vinyl-androstane-30,17B-di0l.

The 3-tctrahydropyranylether of 218-iodo-17avinyl-19norandrostane-3a,17fl-di0l.

Example X I The 3-tetrahydropyranylether of Zfldiuoro-androstan-3e-oi'l7-one was treated by the technique delineated in Example VH1,except that methylmagnesium' bromide was substituted byethi'nyl'maguesium bromide, thus afiording the B-tetrahydmpyranyletherof ZB-du rGUe-ethinyl andrQstane-Se, Uri-dial.

By the same procedure, the starting con-mounds under I were convertedinto the: products under H.

The 3-tetrahydropyranylether of 2B-fluoro-19-nor-andr0stan-3wol- 17-0ne.

The 3-tetrahydropyranylether of Qfi-chloro-androstan-3a-ol-l7-one.

The 3-tetrahydropyranylether of 2 8-chl0ro19-nor-tmdrostau-ba-ol-17-o11e.

The H-tetrahydropyranylether 0f 25-br0mo-andr0stan-3a-ol-17-one.

The 3-tetrahydropyranylethe1 of 2 S-brom0-19-nor-androstau 3a-Ol-17-one.

The 3-tetrahydropyrany1ether of 2fl-iodo-androstau-3a-ol-17-0ne.

The 3-tetrahydropyranylether of 2ti3-iodo-19-nor androstan3a-ol- 1 -one.

The 3-tetrahydropyrauylether of 25-011loro 17a-ethlnyl-androstanc-30:,17/3-di0l.

The 3-tetrahydropyranylether of2B-chlor0-17a-ethinyl-19-noraudr0stane-3a,l7,5-di0l.

The 3-tetrahydropyranylethcr 0t QB-bromo-lM-ethiny1andr0-stane3a,175diol.

The 3-tctrahydropyranylether ofZB-bromo-Ua-cthinyl-lQ-norandrostan-3a,l7fl-diol.

The 3-tetrahydropyranylether of 2B-iod0-17a-ethinyl-androstane3a,17fl-di01.

The 3-tetrahydropyranylether of 25-i0do-17aethinyl-19-norandrostaue-3a,l7fi-diol.

Example XI A mixture of 1 g. of the 3-tetrahydropyranylether of2,8-fluoro androstane-3a,17B-diol, 4 cc. of pyridine and 2 cc. of aceticanhydride was kept at room temperature overnight, poured into ice water,the formed. precipitate was filtered, Washed with water and dried.Crystallization from acetone-hexane gave the B-tetrahydropyranylether of2fl-fluoro-androstane-3oa,17fi-diol-l7-acetate.

Following the above procedure were treated the starting compounds listedbelow, thus producing the hereinafter disclosed products.

Starting 0 ompounds Products The 3-tetrahydropyranylether ofZfl-tluoro-l9-nor-androstane- 3a,17fl-dl01.

The 3-tetrahydropyranylether of ad-tihloro-androstane-h,17B-

The 3-tetral1ydropyranylether of ZB-chloro-19-nor-androstane-304,17fl-di01.

The 3-tetrahydrepyranylether of gfi-hromo-androstaueda,176

The 3-tetrahydropyranylether 0t 2B bromo-19-nor-androstane-3a,17,8-dl0l.

The 3-tetrahydropyranylether of QB-iodo-androstane-3tz,17 6-dio1.

The 3-tetrahydropyranylether of git-if)do-l9-nor-androstane-3a,17fl- TheS-tetrahydropyranylether of 2 8-fluoro-lQ-nor-androstane-3a,17B-dio1-l7aeetate.

The 3-tetrahydropyranylether of 2fi-chloro-audrostane-3a,17H-diol-17-acetate.

The 3-tetrahydropyranylether 0f 2t?-chloro-lQ-norandrostane-3a,17fl-dio1-17-acetate.

The S-tetrahydropyranylether of ZB-bromo-androstane-h,17 9-di0l-17-acetatc.

3-tetrahydropyranylether of 2B- bromo-lQ-nor-androstane-3a,17fi-dio1-17-acetate.

The 3-tetrahydropyranylether of 2B-iodo-androstane-3a,1713-di01-17-acetate.

The 3tetrahydropyranylether of 25-iodo-lQ-nor-androstane- 3a,17;3diol-17-acotate.

Example XII To a solution of 5 g. of the 3-tetrahydropyranylether ducedZfidluoro 17a methyl-androstane-h,17fl-diol-diacetate.

The startingcompounds under I were treated .following the sameprocedure, to produce the corresponding products under TI.

The 3-1;etrahydropyranyl-ether of ZB-fluorol7a-methyl-l9-norandrostane-3a,17/3-dio1.

The 3-tetrahydropyranyhether of 2,6-ehloro-17a-methy1-andro-2fl-fluoro-17a-methy1-19-n0r andrOStaue-Ea,Uri-dieldiacetate.

26-chloro-l7a-methyl-androstan"- 3a,17B-di0l-diacetute.

' ZB-chloro-17a-methyl-androstane-3a, 17f3-dio1,

2/3-chloro-17a-methyl- 19-nor-androstane-3ot,17fl-diol,2fi-bromo-17a-methy1-androstane-311,17,6-di01,2,8-bromo-17a-methyl-19-nor-androstane-3oz, 17,6-dio1,2,6-iodo-17a-methyl-androstane 3u,17fi-diol,2,8-iodo-17a-rnethyl-19-nor-androstane-305,17fl-di0l,2,8-fluoro-17oc-vinyl-androstane-3u,17fi-diol,2fl-fiuoro-17a-vinyl-19-nor-androstane-3a,17;8-diol,ZB-chloro-17ot-vinyl-androstane-3oc,17B-diol,2-fi-Ch10f0-170L-ViI1y1-19-1101wfil1d10SIElIlC-30t,17fl-di0l, Zfi-bromo-1 7a-vinyl androstane-3 oc,17,8=di01,ZB-bromo-l7a-vinyl-19-nor-androstane-3a,l7fl-diol,2,8-iodo-17a-vinyl-androstane-3oa,17B-diol,2B-iodo-17a-vinyl-19-nor-androstane-3a,175-diol,ZB-fluoro-17a-ethinyl-androstane-3a,17,8-diol,2,8-fiuoro-17a-ethinyl-19-nor-androstane-3a,17B-diol,2B-chloro-17a-ethinyl-androstane-3a,17,6-dio1, 28-chloro-17oc-ethinyl-19-nor-androstane-3u,17/3-diol,ZB-bromo-l7ot-ethinyl-androstane-3 a,17,8-diol,

ZB-bromo- 17a-ethinyl- 1 9-nor-androstane-3a, 17 B-diol,

2fi-iodo-l7u-ethinyl-androstane-3a,17/3-diol,ZB-iodo-17a-ethiny1-19-nor-androstane-3a,175-diol.

Example XV A mixture of 1 g. of ZB-fluoroendrostane-h,175-diol- 17acetate 4 cc. of pyridine and 2 cc, of caproic anhydride was kept atroom temperature overnight, poured into ice water, the formedprecipitate was filtered, washed with Water and dried. Crystallizationfrom acetone-hexane gave 2B-fiuoro-androstane-3a,17B-diol-3-caproate-17-acetate.

By the same procedure the compounds obtained in Ex- I ample 13 wereconverted into the following products:

25 fiuoro 19-nor-androstane-3a,17p-d-iol-3-caproate-17- acetate,

2/3 chloro-androstane-3a,17fi-diol-3-caproate-l7-acetate,

2/3 chloro-19-nor-androstane-3a,l7fi-diol-3-caproate-17- acetate,

2B bromo-androstane-3a,17fl diol-3-oaproate-17-acetate,

2 8 bromo-19-nor-androstane-3u,l7fi-diol-3-caproate-l7- acetate,

2,3 iodo-androstane-3u,l7fi-diol-3-caproate-17-acetate,

2B iodo 19-nor-androstane-3a,17,8-di0l-3-caproate-17- acetate,

2t? fluoro-17oc-methyl-androstane-3a,l7l3-diol-3-caproate- 17-acetate,

2B fluoro Hot-methyl-19-nor-androstane-3a,17,6-diol-3-caproate-17-acetate,

2B chloro-17a-methyl-androstane-3a,17/3-diol-3-caproate- 17-acetate, 1

2B chloro 17a-rnethyl-19-nor-androstane-3a,17fl-diol-3-caproate-17-acetate,

2,8 bromo-17ec-methyl-androstane-3a,17B-diol-3-c2iproate- 17-acetate,

2,8 bromo 17u-methyl-19-nor-andr0stane-3a,17B-diol-3-caproate-17-acetate,

2,8 iodo-17a-methyl-androstane-3a,l7l3-diol-3-caproate- 17-acetate,

2B iodo-17a-methyl-19-nor-androstane-3u,17B-diol-3-caproate-17-acetate,

2,8 fiuoro l7a-vinyl-androstane-3a,17B-dio1-3-caproate- 17-acetate,

2,8 fluoro-17ot-vinyl-19-norandrostane-Zwz,1718-diol-3-caproate-17-acetate,

2e chloro-17a-vinyl-androstane-3a,17/i-diol-3-caproate l7-acetate,

2/3chloro-17a-vinyl-l9-nor-androstane-3a,l7,B-diol-3-caproate-17-acetate,

Example X VI A mixture of l g. of 2,8-fiuoro-androstane-3a,l7,8-diol 4cc. of pyridine and 2 cc. of propionic anhydride was kept at roomtemperautre overnight, poured into ice water, the formed precipitate wasfiltered, washed with Water and dried. Crystallization fromacetone-hexane gave 2,8-fluoro-androstane-3a,l'ifi-diol-dipropionate.

By the same procedure the starting compounds under I were converted intothe products under II.

I II

Example XVII The starting compounds of the foregoing example weretreated following the procedure described in the same exampie exceptthat propionic anhydride was substituted by cyclopentylpropionicanhydride, enanthic anhydride and undecanoic anhydride, thus yieldingresriectively the di-cyclopentylpropionates, di-enanthates anddi-undccanoates of said compounds.

Example XVIII To a solution of 5 g. ofZB-fiuoro-l7zx-methyl-androstane-3a,17B-diol in cc. of anhydrous benzenethere were added 1 g. of p-toluenesulfonic acid and 10 cc. of

' propionic anhydride and the mixture was allowed to stand for 24 hoursat room temperature, poured into ice and water, and the resultingmixture stirred to effect hydrolysis of the excess anhydride. Thebenzene layer was separated and washed with 10% sodium carbonatesolution and Water. Drying, evaporation and crystallization of theresidue form ether-hexane produced2B-fiuoro-17amethy1-androstane-3a,l7fl-diol-dipropionate.

By the same technique were treated the starting com- II pounds listedbelow, to produce the corresponding products hereinafter disclosed:

Starting compound Product androstane-3a,17,8-diol.

2fi-chloro-17a-methyl-androstane- 3 l7 diol a B- 23-chlor0-1Ta-lnethyl-lQ-norandrostane-MJTB-drol.

2 3-chloro-17154:thinyl-nndrostane- 2e-bromo-l7a-ethinyl-androstane- 3 1-diol The dipropionate t Qfl-ClllOIO-Uozmethyl-androstane-3a,17fl-di0l.The dipropionate 0f 2,6-0l110I0-17zxmethyl-ltl-nor-androstano-lia,

17B-diol.

The dipropionate oi QB-bromo-IM- methyl-androstane-ita-17Bdi0l. Thedipropionate of 2fl-bromo-17amethyl-l9-n0r-androstane-3a,175-

The dipropionate of 2,8-iodo-17amothyl-androstane-Ba,ITB-diol. 'lhediproprionate of Qfi-iOdO-l'lamothyl-lQ-nor-androstane-Ba,

17fl-diol. The diproprionate of2,5-flllOl'O-17crvinyl-androstane-3a,17B-di0l. The diproprionate012Bfluoro-17a- (viinlyl-w-nor-andr0stane-3a,17B-

The diproprionate oi2fi-ehlor0-17avinyl-androstane-3a,l7fl-diol. Thediproprionate of 2fi-ehloro-l7aginlyl-w-nor-androstrum-3a,17d-

The diproprionate of Qfi-iOdO-l'l'avinyl-androstane-B 176-di0l. Thedipropionate of 2fl-l0(1017agmlyl-ltl'nor-androstime-3a,175-

The dipropionate of 2B-fluoro-17aethinyl-nndrostane-Zia,17,8-di0l. Thedipropionute of 2fi-flLIOr0-17Ctethinyl-19-nor-androstane-3a,17B-

diol.

The dipropionate of 2B-ehl0ro-17aethinyl-androstane-lia,176-(1iol. Thedipropionate of 2 3-eh1oro-17agtltinyl-19-n0r-androstane'3a,17f

The dipropionate of 2B-hromo-17aethinyl-audrostane-3r1,17B-d1ol. Thedipropionate of 2fl-br0m0-17adial.

The dipropionate of 2B-iodo-1Zaethinyl-androstane-3a,17B-diol. Thedipropionate of 2,3-i0d0-17agt hlinylde-nor-androstane-iia,17,6-

Example XIX Following the procedure described in the preceding example,except that propionic anhydride was substituted by enanthic anhydr-ideand cyclopentylpropionic anhydride, the starting compounds mentioned inthe same example, were converted into their respective di-enan thatesand di-cyclopentylpropionates.

12 Example XX I II 2 8-fluoro-19-nor-androstan-3a-ol-17- one.

219-011101-o-19-nor-androstan-3a-ol- The acetate of 2B-ehlor0-androstan-3a,-0l-17-0110. The acetate of ZB-chloro-lQ-norandrostan-3u-o1-17-one.The acetate of 2fi-bromo-androstan- 3a-ol-17-one.

The acetate of 2fi-brom019-norandr0stan-3a-ol-17-one.

The acetate of 2fl-iodo-androstan- 3a-ol-17-o11e.

The acetate of 2/3-i0do-1Qnor-and.ro-

stan-3a-ol-l7-one.

Zfl-bromo-lQ-nor-androstan-3a-o1- 17-one 218-iod0-androstan-3a-ol-17-one2fl-iodo-19-nor-androstan-3a-o1-17- one.

Example XXI The starting compounds mentioned in the foregoing examplewere treated by the procedure described in the same example, except thatacetic anhydride was substituted by propionic anhydride, caproicanhydride and enanthic anhydride thus furnishing the correspondingpropionates, caproates and enanthates.

We claim:

1. A compound of the following formula:

wherein R is lower alkenyl; R and R are selected from the groupconsisting of hydrogen and a hydrocarbon carboxylic acyl group of lessthan 12 carbon atoms; and X is a halogen atom. 1 2.Zfl-fluoro-l7qt-vinyl-19-nor-androstane-3oc,17,8-diol. 3.ZB-chloro-17m-viny1-19-nor-androstane-3 0:,17fi-Hi0ll References Citedin the file of this patent UNITED STATES PATENTS Goldkamp et a1. May 6,1958 3,009,934 Counsell et al. Nov. 21, 1961

1. A COMPOUND OF THE FORMULA: